Drugs Of Second Choice Research Articles

Assessing nystatin cream treatment efficacy against Leishmania (L.) amazonensis infection in BALB/c model

The current scenario for cutaneous leishmaniasis treatment includes the use of first and second-choice drugs, both therapeutic strategies presenting several adverse effects and being related to an increment of treatment-refractory parasite strains. These facts encourage the search for new treatment approaches, including repositioning drugs, such as nystatin. Although in vitro assays show that this polyene macrolide compound has leishmanicidal activity, no in vivo evidence for a similar activity has been shown so far for the commercial nystatin cream formulation. This work assessed the effects of nystatin cream (25,000 IU/g) administered on mice in an amount to completely cover the paw surface of BALB/c mice infected with Leishmania (L.) amazonensis once a day, until a total of up to 20 doses. The data presented herein points to unequivocal evidence that treatment with this formulation causes a statistically significant reduction of swelling/edema in mice paws when compared to animal groups not submitted to this treatment regimen after the fourth week of infection: lesion sizes at the sixth (p = 0.0159), seventh (p = 0.0079) and eighth (p = 0.0079) week. Furthermore, swelling/edema reduction relates to a decrease in parasite load in the footpad (∼48%) and in draining lymph nodes (∼68%) at eight weeks post-infection. This is the first report of the effectiveness of nystatin cream used as a topical treatment in BALB/c model for cutaneous leishmaniasis.

Efficacy of levetiracetam in the treatment of Sydenham chorea.

To study the effect of levetiracetam in treating Sydenham chorea. We retrospectively collected the data of 140 patients diagnosed with Sydenham chorea in the pediatric neurology and pediatric cardiology outpatient clinics of Van Training and Research Hospital between January 2010 and December 2018. There were 140 patients, 102 (70%) of whom were girls, with mean age of onset 11.8±2.7years. Symptomatic treatment was initiated in all patients at the time of diagnosis; this medication was changed during follow up in 15 patients. The most frequently prescribed drugs were haloperidol and sodium (Na) valproate, and the most frequently discontinued one was haloperidol, due to side effects. The second-choice drug was most often levetiracetam. Clinical response often began within the first 2weeks, with Na valproate (P=0.002), within 4weeks with carbamazepine (P=0.037) but 1-6months with haloperidol (P=0.018) and levetiracetam (P=0.008). Time to full remission was similar with Na valproate, carbamazepine, haloperidol, and levetiracetam (P=0.276). Our study indicated that levetiracetam was as effective as the other commonly used drugs in the symptomatic treatment of Sydenham chorea. Levetiracetam might be an option in the treatment of Sydenham chorea because of its acceptable effect and safety profile. This observation needs further support with evidence obtained through controlled and blinded trials.

Quantitative Release Assessment of mcr-mediated Colistin-resistant Escherichia Coli from Japanese Pigs.

Colistin is a critically important antibiotic for humans. The Japanese government withdrew colistin growth promoter and shifted therapeutic colistin to a second-choice drug for pigs in 2017. A quantitative release assessment of mcr-mediated colistin-resistant Escherichia coli (E. coli) in Japanese finisher pigs was conducted under the World Organisation for Animal Health (OIE) risk assessment framework. Input data included colistin resistance and mcr-1-5 test results for E. coli isolates in the Japan Veterinary Resistance Monitoring System (JVARM), postal survey results regarding indication disease occurrence and colistin use by swine veterinarians in 2017 and 2018, and colistin resistance and mcr monitoring experiments at four pig farms in 2017-2018. An individual-based model was developed to assess the risk: the proportion of Japanese finisher pigs with mcr-1-5-mediated colistin-resistant E. coli dominant in the gut on an arbitrary day. Before implementing risk management measures, the risk was estimated to be 5.5% (95% CI: 4.2%-10.1%). At 12 months after stopping colistin growth promoter, the proportion of pigs with plasmid-mediated colistin-resistant E. coli declined by 52.5% on the experiment farms (95% CI: 8.7%-80.8%). The probability of therapeutic colistin use at the occurrence of bacterial diarrhea declined from 37.3% (95% CI: 30.3%-42.5%) in 2017 to 31.4% (95% CI: 26.1%-36.9%), and that of edema disease declined from 55.0% (95% CI: 46.0%-63.7%) to 44.4% (95% CI: 36.9%-52.0%). After risk management implementation, the risk was estimated to have declined to 2.3% (95% CI: 1.8%-4.3%; 58.2% reduction). Scenario analyses showed that pen-level colistin treatment effectively reduces the risk from 5.5% to 4.7% (14.5% reduction), an effect similar to stoppage of therapeutic colistin (16.4% reduction to 4.6%).

Nanoemulsions Loaded with Amphotericin B: Development, Characterization and Leishmanicidal Activity.

Leishmaniasis is one of the most neglected diseases in the world. Its most severe clinical form, called visceral, if left untreated, can be fatal. Conventional therapy is based on the use of pentavalent antimonials and includes amphotericin B (AmB) as a second-choice drug. The micellar formulation of AmB, although effective, is associated with acute and chronic toxicity. Commercially-available lipid formulations emerged to overcome such drawbacks, but their high cost limits their widespread use. Drug delivery systems such as nanoemulsions (NE) have proven ability to solubilize hydrophobic compounds, improve absorption and bioavailability, increase efficacy and reduce toxicity of encapsulated drugs. NE become even more attractive because they are inexpensive and easy to prepare. The aim of this work was to incorporate AmB in NE prepared by sonicating a mixture of surfactants, Kolliphor® HS15 (KHS15) and Brij® 52, and an oil, isopropyl myristate. NE exhibited neutral pH, conductivity values consistent with oil in water systems, spherical structures with negative Zeta potential value, monomodal size distribution and average diameter of drug-containing droplets ranging from 33 to 132 nm. AmB did not modify the thermal behavior of the system, likely due to its dispersion in the internal phase. Statistically similar antileishmanial activity of AmB-loaded NE to that of AmB micellar formulation suggests further exploring them in terms of toxicity and effectiveness against amastigotes, with the aim of offering an alternative to treat visceral leishmaniasis.

ANALYSIS OF THE TREATMENT IN COMBINATION OF ACE INHIBITORS OR ARBS IN THE CARDIOVASCULAR MORTALITY

Objective: To analyze the combination in randomized clinical trials (RCTs) that described the second drug of choice for antihypertensive treatment (angiotensin-converting enzyme inhibitors – ACEIs or angiotensin receptor blockers - ARBs), by intention to treat. Design and method: Systematic review and metanalysis of the RCTs. A database search between 1966 and December 2018 identified eligible RCTs (PubMed, Embase, Scopus, Web of Science/ Web of Knowledge). Risk ratios and their 95% confidence intervals of four outcomes were estimated by a random-effects model. The heterogeneity index of the studies was calculated through I2 test. The risk of bias was assessed using the Risk of Bias (RoB1), from Cochrane Collaboration. All data were analyzed by two independent evaluators (E.B. and B.E.) and the discrepancies were solved by a third evaluator (W.S.B). Results: 46 eligible RCTs were identified. The ACE treatment in combination reduced cardiovascular mortality (−15%), total mortality, stroke and AMI (p < 0.001). The methodological quality of the included studies pointed to an unclear risk of bias. Conclusions: The ACE inhibitors, in combination, present a reduction in cardiovascular mortality, while the ARBs in combination, do not demonstrate this reduction.

Treatment Strategy for Dyslipidemia in Cardiovascular Disease Prevention: Focus on Old and New Drugs.

Prevention and treatment of dyslipidemia should be considered as an integral part of individual cardiovascular prevention interventions, which should be addressed primarily to those at higher risk who benefit most. To date, statins remain the first-choice therapy, as they have been shown to reduce the risk of major vascular events by lowering low-density lipoprotein cholesterol (LDL-C). However, due to adherence to statin therapy or statin resistance, many patients do not reach LDL-C target levels. Ezetimibe, fibrates, and nicotinic acid represent the second-choice drugs to be used in combination with statins if lipid targets cannot be reached. In addition, anti-PCSK9 drugs (evolocumab and alirocumab) provide an effective solution for patients with familial hypercholesterolemia (FH) and statin intolerance at very high cardiovascular risk. Recently, studies demonstrated the effects of two novel lipid-lowering agents (lomitapide and mipomersen) for the management of homozygous FH by decreasing LDL-C values and reducing cardiovascular events. However, the costs for these new therapies made the cost–effectiveness debate more complicated.

Procena preosetljivosti na penicilin - iskustva Klinike za alergologiju i imunologiju Kliničkog centra Srbije

Introduction: Beta(β)-lactam antibiotics are one of the most prescribed medical drugs worldwide. The incidence of self-reported penicillin allergy ranges from 1 to 10 percent. Patients with registered allergy on β-lactam antibiotics are treated with drugs of second choice which are usually more toxic and more expensive. Aim: The aim of this study was to exam the prevalence of penicillin allergy and correlation of clinical, laboratory and socio-demographic characteristic of patients with and without hypersensitivity to penicillin which were available in medical records. Material and methods: This retrospective, descriptive study included consecutive patients, which were treated in Clinic of Allergology and Immunology, Clinical Center of Serbia (CCS), in the period between the years 2010-2015. Anamnestic data of patients with self-reported allergic reaction to penicilin and the rest of β-lactam antibiotics were used, as well as results of in vivo and in vitro tests. Results: 81 patients were evaluated in the study, of which 59 (72.8%) were females. The average age of patients was 41.7±16.47 years. Adverse effects to penicillin were reported by 70/81 (86.4%) tested patients. In accordance with other studies, the most common initial symptoms were rash (exanthema) and angioedema. None of the 70 patients with self-reported allergic reaction to penicillin had positive in vitro tests. Total number of patients with positive in vivo tests is 2/81 (2.5%) Conclusion: Despite a small percentage of positive penicillin hypersensitivity tests of patients with anamnestic data of self-reported allergic reaction, it is necessary to perform in vivo drug provocation test as a gold standard for confirmation of penicillin hypesensitivity in order to reduce the utilization of alternative antimicrobial drugs, the risk of microbial resistance and treatment costs.

Sarkoidóza - nadále záhadné onemocnění

Sarcoidosis is a systemic disease of unknown etiology, characterized by the presence of granulomatous inflammation in affected tissues. In about 90 % it affects the lungs, but it may basically affect any organ, the most frequently the skin, lymph nodes and eyes. In the case of classic lung manifestation this disease is not difficult to diagnose. When dealing with extrapulmonary manifestations, interdisciplinary cooperation is necessary. The treatment of sarcoidosis is needed in about half of the cases, in some 30 % of patients it may change into a chronic stage and possibly lead to serious health problems or premature death. Treatment is commenced following individual evaluation of the extent of the disease and considering its benefit against possible secondary effects. Corticosteroids remain the systemic drugs of first choice. When ineffective or not tolerated, the drugs of second choice are given, these are corticosteroid replacement drugs such as methotrexate, antimalarial drugs and immunosuppressive drugs. For refractory forms, biological therapy is administered, in particular infliximab or adalimumab.Key words: biological therapy - corticosteroids - corticosteroid replacement treatment - extrapulmonary lesions - sarcoidosis.

Tyrosine kinase inhibitors in chronic myeloid leukaemia: which, when, for whom?

The therapeutic armamentarium for chronic myeloid leukaemia (CML) comprises mainly tyrosine kinase inhibitors (TKIs), with several agents available for frontline treatment, or for the treatment of disease resistance or intolerance to the first-choice or second-choice drug. The availability of different drugs is a major achievement, but means that choices must be made - which can be difficult and questionable at times. The most important end point considered in decision-making regarding treatment for any cancer is overall survival, but additional factors (such as age, prognostic category, safety, or the possibility of achieving treatment-free remission) should be considered when selecting an agent for frontline treatment. Regardless of the TKI selected for first-line treatment, guidelines that define the importance of reaching specific response indicators and procedures for vigilant follow-up monitoring are established to ensure timely implementation of second-line TKIs. Herein, we discuss the benefits and risks of the different TKIs available for the treatment of patients with CML, and how to decide when to employ these agents at different treatment settings.

Mycobacterium tuberculosis-Secreted Tyrosine Phosphatases as Targets Against Tuberculosis: Exploring Natural Sources in Searching for New Drugs.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), which primarily affects the respiratory tract. Combinations of drugs are used for therapeutic synergism and to prevent the emergence of drug resistant strains, but even first- or secondchoice drugs present some disadvantages, such as significant side effects and the need for long duration of treatments. Thus, new strategies for TB control and treatment are highly demanded. In this context, protein tyrosine phosphatases (PtpA and PtpB) are secreted by Mtb within the host macrophage and they have been shown to contribute to Mtb pathogenicity. The understanding of the role of these PTPs has led to interesting anti-TB drugs discovery. Here, we review the current knowledge on these two proteins as targets for novel anti-TB therapies, with particular emphasis on their mechanism of action and current advancements in developing small molecule inhibitors from natural sources.

Epilepsy treatment: precision medicine at a crossroads

In this issue of The Lancet Neurology, David Goldstein and colleagues of the EpiPM Consortium 1 EpiPM ConsortiumA roadmap for precision medicine in the epilepsies. Lancet Neurol. 2015; (published online Sept 21.)http://dx.doi.org/10.1016/S1474-4422(15)00199-4 Google Scholar provide a challenging view of how genetic and molecular biological tools could advance the search for therapeutic targets in epilepsy that are specific for each patient's genetic constitution. Despite the various structures and mechanisms of action of currently available antiepileptic drugs, many patients are still not seizure-free or have adverse drug reactions. Guidelines exist for drugs of first and second choice on the basis of current epilepsy classifications, yet the added therapeutic value of most new compounds is somewhat limited, and antiepileptic drug treatment is still typically a matter of trial and error. This situation might improve with better insight into the individual genetic determinants of disease and therapeutic responses, thus driving research into individually tailored treatments for patients with epilepsy. 1 EpiPM ConsortiumA roadmap for precision medicine in the epilepsies. Lancet Neurol. 2015; (published online Sept 21.)http://dx.doi.org/10.1016/S1474-4422(15)00199-4 Google Scholar A roadmap for precision medicine in the epilepsiesTechnological advances have paved the way for accelerated genomic discovery and are bringing precision medicine clearly into view. Epilepsy research in particular is well suited to serve as a model for the development and deployment of targeted therapeutics in precision medicine because of the rapidly expanding genetic knowledge base in epilepsy, the availability of good in-vitro and in-vivo model systems to efficiently study the biological consequences of genetic mutations, the ability to turn these models into effective drug-screening platforms, and the establishment of collaborative research groups. Full-Text PDF

Therapy of trigeminal autonomic headaches

Trigeminal autonomic cephalgias (TAC) are characterized by severe and strictly unilateral headaches with a frontotemporal and periorbital preponderance in combination with ipsilateral cranial autonomic symptoms, such as lacrimation, conjunctival injection, rhinorrhea, nasal congestion, and restlessness or agitation. One main differentiating factor is the duration of painful attacks. While attacks typically last 5s to 10min in SUNCT syndrome (short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing), paroxysmal hemicrania lasts 2-30min and cluster headaches 15-180min. Hemicrania continua represents a continuous TAC variant. From a therapeutic view, TACs differ substantially. Lamotrigine is used as first-choice prevention in SUNCT syndrome and indometacin in paroxysmal hemicrania. For cluster headaches, acute therapy with inhaled pure oxygen and fast-acting triptans (sumatriptan s.c. and intranasal zolmitriptan) is equally important to short-term preventive therapy with methysergide and cortisone and long-term prophylactic treatment comprising verapamil as drug of first choice and lithium carbonate and topiramate as drugs of second choice. In refractory cases of chronic cluster headache, neuromodulatory approaches such as occipital nerve stimulation and sphenopalatine ganglion stimulation are increasingly applied.

Year in review 2012: Asthma and chronic obstructive pulmonary disease

Year in review 2012: Asthma and chronic obstructive pulmonary disease

Identification of Antibiotics used in Clinical Surgery and Orthopedic Unit from Midsized Hospital in Mato Grosso

Abstract: This study aimed to identify the pattern of antimicrobial use in a unit and orthopedic surgical clinic of a medium-sized hospital in Mato Grosso. The study based in analysis of 500 medical charts and filling out forms previously prepared from Regional Hospital of Sorriso, between March and April 2012, after approval of the project by CEP Julio Muller University Hospital (Protocol No. 219/2011). It was observed that 69% (345) of the sample were male, with ages ranging between 18 and 112 years. In all the charts can observe the prescription of antibiotics, the most prescribed the cephalothin 49.2% (297), Amikacin 12.27% (74) 5.3% Gentamicin (32), Ciprofloxacin 4.31 % (26) and Clindamycin 3.31% (20). Among the 500 records analyzed only 9 (1.8%) underwent antimicrobial prophylaxis and 491 (98.2) did not receive prophylaxis. Among the antimicrobials used in surgical prophylaxis met the cephalothin, used in 77.8% of cases and Clindamycin in 22.2% of cases, these drugs of second choice within the parameters of the National Health Surveillance Agency (ANVISA). The rational use of antibiotics reduce any risk of emergence of resistant microbial strains and still be profitable in terms pharmacoeconomics Keywords: Antimicrobial; Surgical Clinic, Nursing; Antibiotic.

In vitro effect of three-drug combinations of antituberculous agents against multidrug-resistant Mycobacterium tuberculosis isolates

Multidrug resistance has become a problem in the management of tuberculosis, leading to an urgent need for research related to new regimens including the currently available drugs. The objectives of this study were: (i) to study the effect of the following second-choice three-drug combinations against multidrug-resistant (MDR) and drug-susceptible clinical isolates (levofloxacin, linezolid and ethambutol; levofloxacin, amikacin and ethambutol; and levofloxacin, linezolid and amikacin); and (ii) to compare the effect of these combinations with an isoniazid, rifampicin and ethambutol combination against drug-susceptible clinical isolates. A total of 9 MDR clinical and 12 drug-susceptible isolates (11 clinical isolates and the H37Rv reference strain) were studied using an adaptation of the chequerboard assay. The fractional inhibitory concentration index (FICI) was calculated as follows: FICI=FICA+FICB+FICC=A/MICA+B/MICB+C/MICC, where A, B and C are the minimum inhibitory concentrations (MICs) of each antibiotic in combination and MICA, MICB and MICC are the individual MICs. The FICI was interpreted as synergism when the value was <0.75. The FICI of all the combinations ranged from 1.5 to 3, showing indifferent activity. No differences were found between MDR and drug-susceptible isolates, or between the second-choice combinations and the fourth combination against drug-susceptible isolates. In conclusion, the second-choice drugs are equally effective as the combination of isoniazid, rifampicin and ethambutol.

Enterococcus and Streptococcusspp. associated with chronic and self-medicated urinary tract infections in Vietnam

BackgroundUrinary tract infections (UTI) are one of the most common infections among women worldwide. E. coli often causes more than 75% of acute uncomplicated UTI, however, little is known about how recurrent UTIs and indiscriminate use of antimicrobials affect the aetiology of UTIs. This study aimed to establish the aetiology of UTI in a population of recurrent and self-medicated patients referred from pharmacies to a hospital in Hanoi, Vietnam and to describe genotypes and antimicrobial susceptibility of the associated bacterial pathogens. The aetiology of bacterial pathogens associated with UTI (defined as ≥ 104 CFU/ml urine) was established by phenotypic and molecular methods. Enterococcus faecalis isolates were typed by Multi Locus Sequence Typing (MLST), Pulsed-Field Gel Electrophoresis (PFGE) and antimicrobial susceptibility testing.MethodsUrine samples from 276 patients suffering symptoms of urinary tract infection were collected and cultured on Flexicult agar® allowing for detection of the most common urine pathogens. Patients were interviewed about underlying diseases, duration of symptoms, earlier episodes of UTI, number of episodes diagnosed by doctors and treatment in relation to UTI. All tentative E. faecalis and E. faecium isolates were identified to species level by PCR, 16S rRNA and partial sequencing of the groEL gene. E. faecalis isolates were further characterized by Multi Locus Sequence Typing and antimicrobial susceptibility testing.ResultsMean age of 49 patients was 48 yrs (range was 11–86 yrs) and included 94% women. On average, patients reported to have suffered from UTI for 348 days (range 3 days-10 years, and experienced 2.7 UTIs during the previous year). Cephalosporins were reported the second drug of choice in treatment of UTI at the hospital. E. faecalis (55.1%), E. coli (12.2%) and Streptococcus gallolyticus subsp. pasteurianus (8.2%) were main bacterial pathogens. MIC testing of E. faecalis showed susceptibility to ampicillin, penicillin and vancomycin, but high-level resistance against gentamicin (48.1%). MLST revealed 12 Sequence Types (ST) of which ST 16 made up 44.5% and showed closely related PFGE types.ConclusionThe different aetiology of UTI compared with reports elsewhere, where E. coli dominates, may be a result of chronic and recurrent UTIs together with indiscriminate use of antimicrobials. The similar genotypes shown by epidemiologically unrelated ST 16 isolates in Vietnam and elsewhere, suggest that E. faecalis ST 16 might represent a globally distributed clone. Treatment of UTI with cephalosporins may select for E. faecalis as it is intrinsic resistant and further studies are needed to establish the source(s) and role of E. faecalis ST 16 in acute UTI.

Situation of infection by M. Tuberculosis in a spanish tertiary care hospital

BackgroundNowadays tuberculosis continues to be a global public health problem. In 2009, 6,131 cases of respiratory tuberculosis were notified in Spain, making it the 8th European country with the highest...

Comparison of biologics as drugs of second choice from patients for RA

Comparison of biologics as drugs of second choice from patients for RA

Therapy of Hyperthyroidism in Pregnancy and Breastfeeding

Uncontrolled hyperthyroidism in pregnancy is associated with an increased risk of perinatal complications. The state of the art discussed here has been derived through a wide MEDLINE search throughout English-language literature by using a combination of words such as hyperthyroidism, propylthiouracil (PTU), methimazole, rituximab, and pregnancy to identify original related works and review articles. Thioamides are the main first-line therapeutic options, whereas beta-blockers and iodine are second-choice drugs; surgery is resorted to only in exceptional cases. Methimazole and PTU reduce the production of thyroid hormones by selectively inhibiting thyroid peroxidase. PTU was once considered to be the first-choice drug in the treatment of gestational hyperthyroidism; however, the United States Food and Drug Administration now recommends it as a second-line thioamide, which should be used solely by women in their first trimester of pregnancy. Thyroidectomy is to be carried out only in pregnant women affected by life-threatening, uncontrollable hyperthyroidism, or in cases with thioamide intolerance. Obstetricians & Gynecologists, Family Physicians After completion of this article, the physician should be better able to choose appropriate therapies for hyperthyroidism in pregnant women, assess the risk of possible complications due to maternal hyperthyroidism, and evaluate strategies for patient follow-up.

Antimicrobial susceptibilities of Listeria monocytogenes human strains isolated from 1970 to 2008 in Brazil

Listeria monocytogenes is the causative agent of listeriosis, a foodborne illness that affects mainly pregnant women, the elderly and immunocompromised patients. The primary treatment is a combination of ampicillin with an aminoglycoside, in addition to a second-choice drug represented by chloramphenicol, erythromycin, tetracycline and rifampicin. The aim of this study was to analyze the antimicrobial susceptibility profile of strains isolated from human sources in the last four decades. Sixty-eight strains were selected from the culture collection of the Laboratory of Bacterial Zoonoses/LABZOO/FIOCRUZ isolated in different regions of Brazil from 1970 to 2008 and primarily isolated from cerebrospinal fluid and blood culture. Susceptibility tests to antimicrobials drugs were evaluated using the criteria established by Soussy using the Kirby-Bauer method and E-Test strips were used to determine the minimum inhibitory concentration (MIC). Among the strains tested, serovar L4b (60.3%) was the most prevalent, followed by serovar 1/2a (20.6%), 1/2b (13.2%) and the more uncommon serovars 1/2c, 3b and 4ab (5.9%). All strains were susceptible to ampicillin, cephalothin, erythromycin, gentamicin, teicoplanin and vancomycin. Only one strain (1.5%) showed resistance to rifampin, and two (3%) were resistant to trimethoprim-sulfamethoxazole. MICs with values up to 2 μg/ml reinforce the need for microbiological surveillance. The study demonstrated low prevalence of strains resistant to the antimicrobial drugs indicated in the treatment of human listeriosis. Monitoring antimicrobial resistance profile is still very important to determine adequate treatment, especially in immunocompromised patients.